The general aims are: 1) to maintain a group of laboratory and clinical investigators who can interrelate their research in such a way as to investigate and resolve problems related to clinical cerebrovascular disease, 2) to develop techniques and models to simulate clinical cerebrovascular disease so that pathogenesis, temporal sequence of pathophysiological changes, and sequence of molecular alterations can be studied to determine the stage at which reversibility of ischemia is possible and to study what processes or agents may aid in producing reversal of the ischemic process, 3) to study the natural history of cerebrovascular diseases and to determine whether forms of standard management have altered natural history, by using the resources of the Rochester epidemiological, and 4) to maintain an environment for training individuals for careers of leadership center research, teaching, and clinical service in cerebrovascular disease. Laboratory research will include study of the molecular mechanism of ischemia and anoxia, the study of the pathophysiology of regional cerebral ischemia and the effect of induced hypertension and hypotension. Measurement of the fluorescence of reduced nicotinamide adenine nucleotide (NADH) has been used to study the effects of anesthetic agents and variations in carbon dioxide tensions on ischemic and anoxic cerebral tissue in living animals. Clinical studies will be carried out using the integrated Mayo medical record system for the city of Rochester and for Olmsted County. Studies of the carotid and cerebral circulation will be done with a recently developed ultrasonic B-scanner and by pulsatile echoencephalography. Studies of cerebral ischemic lesions in humans will be furthered by an image analysis program and the use of computerized $ tomography of the head.